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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neonatal hematopoiesis and host defense are developmentally immature and under states of increased demand predispose the newborn to peripheral cytopenias and depletion of bone marrow storage pool reserves. We have previously demonstrated that recombinant human granulocyte colony-stimulating factor (rhG-CSF) can significantly modulate neonatal rat granulopoiesis and act synergistically with antibiotic therapy to reduce the mortality rate during experimental group B streptococcal sepsis. Stem cell factor (SCF) has been shown to stimulate early hematopoietic progenitor cells and, in the presence of lineage-specific CSFs, enhance committed progenitor cell proliferation. In the present study we examined the in vivo neonatal hematologic effects of recombinant rat (rr) SCF (14 days), simultaneous rrSCF + rhG-CSF (14 days), and sequential combination of rrSCF (7 days) + rhG-CSF (7 days). Sprague-Dawley newborn rats (less than or equal to 24 hours) were injected intraperitoneal (IP) x 14 days with the above combinations. rrSCF (0 to 200 micrograms/kg/d) had a negligible effect on the peripheral platelet count and absolute neutrophil count (ANC) but the diminution in the hematocrit during the first 10 days of treatment was less pronounced (P = .0001). However, the simultaneous use of rrSCF + rhG-CSF synergistically increased the circulating day 6 to 13 ANC (P = .001). Similarly, sequential rrSCF + rhG-SCF also had a synergistic significant effect during the second week of therapy on the circulating ANC (P = .01). The bone marrow neutrophil storage and proliferative pools were also significantly increased in newborn rats treated with rrSCF + rhG-CSF versus rhG-CSF (P = .02). The bone marrow and liver/spleen CFU-GM pool was unchanged; however, the CFU-GM proliferative rates were significantly increased in the rrSCF + rhG-CSF group (P = .04). rrSCF also induced a significant increase in the bone marrow and liver/spleen mast cell pool (P = .002). Lastly, rrSCF x 14 days +/- rhG-CSF significantly reduced the mortality rate at 48 and 120 hours after experimental group B streptococcus sepsis (P = .03 and .05, respectively). These data suggest that combination SCF + G-CSF therapy compared with G-CSF alone significantly increases the neonatal rat peripheral neutrophil count, bone marrow myeloid pools and proliferative rates, and induces a reduction in the mortality rate during experimental bacterial sepsis. SCF therapy may have future potential applications in the modulation of human neonatal hematopoiesis and host defense.
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PMID:Effect of stem cell factor with and without granulocyte colony-stimulating factor on neonatal hematopoiesis: in vivo induction of newborn myelopoiesis and reduction of mortality during experimental group B streptococcal sepsis. 137 57

We investigated the effects of repetitive recombinant human granulocyte colony-stimulating factor (rhG-CSF) administration at three different doses (every 12 h times six doses, starting at 12-24 h of age) on the kinetics of neutrophil production in Sprague-Dawley rats. We determined WBC counts, differentials, the number of total nucleated cells, the myeloid mitotic pool cells (promyelocytes and myelocytes), the storage pool cells (metamyelocytes, bands, and polymorphonuclear cells [PMNs]) and the granulocyte-macrophage (granulocyte-macrophage colony-forming units, CFU-GM) and macrophage (macrophage colony-forming units, CFU-M) progenitor cells of the bone marrow, spleen, and the liver before the first dose of rhG-CSF administration and 12 h after the second, fourth, and sixth dose. Control animals were given the diluent by the same schedule. Recombinant human G-CSF-treated rats showed a significant dose-dependent increase in the number of total WBC and neutrophil counts at all time points compared to control rats. The total number of CFU-GM and myeloid mitotic pool cells (marrow plus spleen plus liver) progressively increased with age in both control and G-CSF groups, but the G-CSF treated groups showed a significantly larger number of mitotic pool cells at hour 24, continuing up to hour 72, compared to the control group. However, there was no significant difference at any time point in the number of CFU-G/GM as detected by the granulocyte-macrophage colony-stimulating factor (GM-CSF)-supported culture system. Priming of newborn rats with injections every 12 h of rhG-CSF times two doses, or six doses followed by inoculation of group B streptococci (GBS) did not significantly change the sepsis death rate of animals, although the neutrophil counts in infected rhG-CSF-primed animals were significantly larger than the infected control animals. Injection of human i.v. gammaglobulin 3 h following inoculation with GBS significantly improved the survival of animals compared to G-CSF administration or administration of the diluent alone (control). Thus G-CSF alone may not be beneficial for the treatment of neonates with sepsis. Additional work is needed to determine whether combination of G-CSF with antibiotics or other cytokines, such as GM-CSF or interleukin 6 (IL-6) may be of benefit.
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PMID:Effect of recombinant human granulocyte colony-stimulating factor administration in normal and experimentally infected newborn rats. 170 9

A seventy-five-year-old female with general fatigue, high fever and anemia was admitted. Her chest X-ray film revealed pneumonia. She was diagnosed as RAEB-t with the normal karyotype by peripheral blood film and bone marrow aspiration; 125 micrograms/ml of G-CSF was administered s.c. daily in order to increase neutrophil count because of the prolongation of pneumonia. Her blast cells in both peripheral blood and bone marrow showed a remarkable increase by G-CSF. After the cessation of G-CSF administration, blast cells decreased rapidly, and neutrophil count in the peripheral blood increased. Her pneumonia was then cured. After 5 months of stable hematological state, 60% of her bone marrow cells became occupied by blast cells again. So 2 consecutive courses of 14 days p.o. administration of 1,200 mg MST-16/day were tried. Three months after the first MST-16 trial, her bone marrow showed complete remission (CR) which lasted about 4 months. But she died of sepsis after the first relapse. Her bone marrow in CR still revealed several features of dyspoiesis.
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PMID:[A case of RAEB-t treated by G-CSF showing complete remission after MST-16 treatment for subsequent reversible leukemia]. 171 93

Severe thermal injury results in impairment of granulocyte production and function. The ability to improve the functional capacity of neutrophils could contribute to a reduced morbidity and mortality from sepsis following thermal injury. Previous studies from this laboratory have shown that rhG-CSF increases the number of femoral marrow granulocyte progenitor cells and circulating neutrophils as well as the survival rate following burn wound infection. The studies reported here examine the effect of in-vivo administration of rhG-CSF on neutrophil chemotaxis following a burn injury and also following superimposed Pseudomonas burn wound sepsis in mice. Casein-elicited peritoneal neutrophils were harvested 72 hours after burn injury and 24 hours after infection. Chemotaxis was assessed using microchemotaxis chambers and 10(-5) M fMet-Phe as a chemoattractant. The number of neutrophils that migrated into the filter was used as an index of directed chemotaxis. Burn injury resulted in depressed chemotaxis compared with sham or sham/G-CSF-treated animals (p less than 0.05). Administration of rhG-CSF to burned animals resulted in a level of neutrophil chemotaxis comparable with that in control animals. The presence of a burn wound infection caused no further impairment of chemotaxis. Administration of rhG-CSF to animals with a burn wound infection resulted in improved chemotaxis compared with sham, burned, and burned/infected animals. The beneficial effect of G-CSF following burn wound infections from this and previous studies appears to be a combination of expanded numbers of myeloid elements and preservation of their function.
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PMID:The effect of granulocyte colony-stimulating factor (G-CSF) upon burn-induced defective neutrophil chemotaxis. 202 39

Haemopoietic growth factors (HGFs) are being administered to patients with neutropenic fever; however, little is known about the endogenous HGF response in these patients. Specific assays were used to study four HGFs, granulocyte (G-) CSF, granulocyte-macrophage (GM-) CSF, macrophage (M-) CSF and interleukin (IL-) 6 levels in the blood of patients with neutropenic fever (46 episodes). For comparison, levels were also measured in three control populations: normals (20), afebrile neutropenic (14), and bacteraemic but not neutropenic patients (20). In febrile patients, levels of G-CSF (median, range) (0.46, < 0.10-142 ng/ml). IL-6 (0.054, 0.005-24.3 ng/ml) and M-CSF (18.5, 9.9-79.1 ng/ml) were elevated compared with afebrile subjects (< 0.10, < 0.10-1.62 ng/ml). (0.008, 0.002-0.024 ng/ml) and (6.45, < 5.0-31.3 ng/ml) respectively. GM-CSF was not elevated (< 0.02, < 0.02-8.0 ng/ml) compared with afebrile subjects (0.021, < 0.02-0.20 ng/ml). Variables significantly associated (P < 0.05) with elevated cytokine levels were determined by multiple regression analyses. Factors associated with G-CSF elevation were fever, neutropenia, pathogen type and raised bilirubin and creatinine. In contrast, neutropenia was not associated with IL-6 elevation although there was an association between IL-6 elevation and fever, Gram-negative and fungal infections and raised creatinine and bilirubin. M-CSF elevation was associated with fever, renal impairment and known pathogen. Elevated G-CSF and IL-6 levels normalized rapidly (hours-days) with the resolution of infection, whereas M-CSF concentrations remained elevated for up to 10 d. Cytokine levels remained elevated in septic neutropenic patients who did not recover. In summary, G-CSF, IL-6 and M-CSF levels were significantly elevated in sepsis. In contrast, GM-CSF levels were not elevated. These studies should assist the development of therapeutic strategies using HGFs in the treatment of sepsis.
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PMID:Endogenous haemopoietic growth factors in neutropenia and infection. 751 65

A study was carried out to investigate the efficacy of therapy with recombinant human granulocyte colony-stimulating factor (rhG-CSF) in 24 patients with granulocytopenia and sepsis who had failed to respond to antibiotics. The mean leukocyte count at the start of the study was 911 +/- 334/microliter. Patients were injected subcutaneously with 75 micrograms rhG-CSF once daily for a mean of 5.2 days. The plasma G-CSF concentration was measured by ELISA. The leukocyte count increased approximately 9-fold after 1 week in 19 patients and the percentage of granulocytes rose from 46.2% to 78.9%. These 19 patients survived, while the 5 patients with no leukocyte response to rhG-CSF died. High plasma G-CSF levels were found in patients with granulocytopenia. Plasma G-CSF levels decreased as levels of granulocyte increased in survivors. A high plasma G-CSF concentration persisted in the 5 non-responding patients resulting in a fatal outcome. This study suggests that rhG-CSF both increased the leukocyte count and was a useful therapeutic manoeuvre for sepsis.
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PMID:Evaluation of recombinant human granulocyte colony-stimulating factor (rhG-CSF) therapy in granulopoetic patients complicated with sepsis. 753 91

A combination antibacterial therapy with fosfomycin (FOM) and sulbactam/cefoperazone (SBT/CPZ) was applied to 78 patients with severe infections associated with hematological diseases. In this protocol, FOM was followed by SBT/CPZ and each drug was administered for 1 hour intravenously and consecutively. Among 72 evaluable patients, 43 patients had acute leukemia, myeloblastic or lymphoblastic, 22 had malignant lymphoma, 3 had multiple myeloma, and 4 had other hematological diseases as underlying diseases. Bacterial infections diagnosed were sepsis in 21 patients, suspected sepsis in 47, and other infections in 4. The overall efficacy rate of this treatment was 72.2%, and those for individual infections were 66.7% for sepsis, 74.5% for suspected sepsis, and 75.0% for other infectious diseases. Among 22 bacteria separated from patients with sepsis, 78.6% (11/14 strains) were eradicated by this treatment. This protocol was also effective in 57.1% (8/14) of patients whose granulocyte count was less than 100/mm3 during the course of treatment as well as in 83.3% (15/18) of patients with granulocyte count over 500/mm3. There was no difference in effectiveness between those patients to whom G-CSF was administered and those to whom it was not (17/24, 70.8% vs 35/48, 72.9%). As an adverse reaction, a transient increase of GOT and/or GPT was observed in 2 patients (2.8%). The consecutive administration treatment of FOM and SBT/CPZ is thus an effective and safe regimen for the treatment of patients with hematological diseases complicated by severe infections.
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PMID:[A combined consecutive therapy with fosfomycin and sulbactam/cefoperazone for bacterial infections associated with hematological diseases]. 754 Feb 19

Hyper-IgM syndrome associating with severe neutropenie presenting in irregularis cycles was diagnosed in a 3-year-old male patient. His elder brother died of sepsis which appeared as a consequence of dysgammaglobulinaemia and neutropenia at the age of 9. We could not achieve a parmanent good result with the monthly immunoglobulin substitution and supportive treatment. The candida infection of the gingiva and of the oral mucous membrane expanded to the esophagus resulting in its complete occlusion and temporarily a gastrostomy was needed to feed him. We started with the recombinant human granulocyta colony stimulating factor (rh-G-CSF) treatment at the age of 6. We tried several ways of applying and finally the 10 micrograms/kg/dose given subcutan, for 5-10 days from the nadir of the neutropenic cycle seemed the most effective. The rh-G-CSF treatment resulted in an increase of ANC and the complete resolution of gingivostomatitis. The incidents of infections, the requirement of antibiotics and the duration of hospitalisation were markedly reduced. The consequent improvement in his physical condition made it possible to finally resolve the esophageal stricture surgically. We have not observed any neutropenic cycle since the end of the 14 month rh-G-CSF treatment. Though the medicine was discontinued there has been no recidiva for more than 22 months.
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PMID:[Successful treatment of cyclic neutropenia associated with hyperimmunoglobulin M syndrome using recombinant granulocyte-colony stimulating factor]. 756 51

Reproducible and characteristic clinical findings of fever, skin rash, capillary leak and pulmonary infiltrates have been observed during engraftment in patients with autologous bone marrow (BM) and/or peripheral stem cell transplantation (PSCT). Two hundred and forty-eight patients were analyzed retrospectively to establish the clinical entity, to characterize the clinical course, and to find clinical variables affecting the incidence of the syndrome. One hundred and eight cases (83.7 +/- 9.4%) of fevers occurring in the periengraftment period (PEN) not associated with positive cultures, biopsies, or clinical signs of infection did not reveal delayed documentation of concealed infection in 2 weeks after engraftment. Capillary leak, pulmonary infiltrates, hypoxia, non-infectious neutropenic fever of engraftment and skin rash were found to be interrelated (all P < 0.01 except for hypoxia vs rash; P < 0.05). By stepwise discriminant analysis, one hundred and thirty-two patients (58.9 +/- 6.4%) were shown to have both skin rash and non-infectious neutropenic fever, thereby constituting the syndrome. Sepsis in the first week of neutropenia decreased the incidence of the syndrome (58.5 +/- 7.7% with sepsis, 89.6 +/- 4.7% without sepsis, P < 0.01). Post-transplant granulocyte colony-stimulating factor increased the incidence of the syndrome (79 +/- 4.6% with G-CSF vs 48.3 +/- 8.2% without G-CSF, P < 0.01). In bone marrow transplantation (BMT), the median time of onset of the syndrome was 7 days (range 4-22 days) post-transplant with a median duration of 11 days (range 4-28 days) of the initial phase. Thirty-nine patients (17.4 +/- 5.0%) revealed a recurrent pattern during the 5th week post-transplant.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Engraftment syndrome in autologous bone marrow and peripheral stem cell transplantation. 758 Nov 19

Haematopoietic growth factors help patients with intense chemotherapy and patients after transplantation of bone marrow to overcome the critical stage of leucopenia. In the submitted paper the authors present more detailed data on the results of investigations evaluating G-CSF, GM-CSF and erythropoietin in patients with anti-tumourous treatment. Both leucocytic growth factors, G-CSF and GM-CSF shorten the period of leucopenia by approximately one week which means a substantial reduction of the number of infectious complications and also a reduction of the hospitalization period. The price of the mentioned growth factors which is still high as compared with the costs of intensive treatment of septicaemia in leukopenic patients. To the authors' surprise, comparing an equal period of time, treatment of septicaemia is associated with much higher costs than administration of G-CSF which can prevent sepsis or reduce its duration.
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PMID:[Hematopoietic growth factors in antineoplastic therapy from the therapeutic and economic aspect]. 768 19


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